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Cancers 2019, 11(4), 545; https://doi.org/10.3390/cancers11040545

Identification of KIF11 as a Novel Target in Meningioma

1
Division of Experimental Neurosurgery, Department of Neurosurgery, University of Heidelberg, INF 400, D-69120 Heidelberg, Germany
2
Department of Radiation Oncology, University of Heidelberg, INF 400, D-69120 Heidelberg, Germany
3
Department of Clinical Pathology, Suez Canal University, 41522 Ismailia, Egypt
4
Department of Neuropathology, Institute of Pathology, University of Heidelberg, German Cancer Consortium, CCU Neuropathology, German Cancer Research Center, INF 224, D-69120 Heidelberg, Germany
5
Department of Neurosurgery, University Medical Center Hamburg Eppendorf, Martinistr 52, D-20246 Hamburg, Germany
6
Department of Neurosurgery, University Hospital, Goethe University, Schleusenweg 2, D-60528 Frankfurt am Main, Germany
7
Department of Neurosurgery, University Hospital Wuerzburg, Josef-Schneider-Str 2, D-97080 Wuerzburg, Germany
8
Department of Neurosurgery, Saarland University, Medical School, Kirrberger Str, D-66421 Homburg, Germany
9
Department of Neurosurgery, Bethel Clinic, Burgsteig 13, D-33617 Bielefeld, Germany
*
Author to whom correspondence should be addressed.
Received: 14 March 2019 / Revised: 9 April 2019 / Accepted: 11 April 2019 / Published: 15 April 2019
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Abstract

Kinesins play an important role in many physiological functions including intracellular vesicle transport and mitosis. The emerging role of kinesins in different cancers led us to investigate the expression and functional role of kinesins in meningioma. Therefore, we re-analyzed our previous microarray dataset of benign, atypical, and anaplastic meningiomas (n = 62) and got evidence for differential expression of five kinesins (KIFC1, KIF4A, KIF11, KIF14 and KIF20A). Further validation in an extended study sample (n = 208) revealed a significant upregulation of these genes in WHO°I to °III meningiomas (WHO°I n = 61, WHO°II n = 88, and WHO°III n = 59), which was most pronounced in clinically more aggressive tumors of the same WHO grade. Immunohistochemical staining confirmed a WHO grade-associated upregulated protein expression in meningioma tissues. Furthermore, high mRNA expression levels of KIFC1, KIF11, KIF14 and KIF20A were associated with shorter progression-free survival. On a functional level, knockdown of kinesins in Ben-Men-1 cells and in the newly established anaplastic meningioma cell line NCH93 resulted in a significantly inhibited tumor cell proliferation upon siRNA-mediated downregulation of KIF11 in both cell lines by up to 95% and 71%, respectively. Taken together, in this study we were able to identify the prognostic and functional role of several kinesin family members of which KIF11 exhibits the most promising properties as a novel prognostic marker and therapeutic target, which may offer new treatment options for aggressive meningiomas. View Full-Text
Keywords: meningioma; KIF; kinesin; KIF11; NCH93 meningioma; KIF; kinesin; KIF11; NCH93
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Jungwirth, G.; Yu, T.; Moustafa, M.; Rapp, C.; Warta, R.; Jungk, C.; Sahm, F.; Dettling, S.; Zweckberger, K.; Lamszus, K.; Senft, C.; Loehr, M.; Keßler, A.F.; Ketter, R.; Westphal, M.; Debus, J.; von Deimling, A.; Simon, M.; Unterberg, A.; Abdollahi, A.; Herold-Mende, C. Identification of KIF11 as a Novel Target in Meningioma. Cancers 2019, 11, 545.

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